Blinatumomab

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Blinatumomab ?
Monoclonal antibody
Type Bi-specific T-cell engager
Source Mouse
Target CD19, CD3
Clinical data
Legal status
?
Identifiers
CAS number 853426-35-4 N
ATC code None
UNII 4FR53SIF3A YesY
Chemical data
Formula C2367H3577N649O772S19 
Mol. mass 54.1 kDa
 N (what is this?)  (verify)

Blinatumomab (AMG103) is a drug that has anti-cancer properties. It belongs to a new class of constructed monoclonal antibodies, bi-specific T-cell engagers (BiTEs), that exert action selectively and direct the human immune system to act against tumor cells. Blinatumomab specifically targets the CD19 antigen present on B cells.[1]

The drug was developed by a German-American company Micromet, Inc. in cooperation with Lonza; Micromet was later purchases by Amgen, which has furthered the drug's clinical trials. In July 2014, the FDA granted breakthrough therapy status to blinatumomab for the treatment of acute lymphoblastic leukemia (ALL).[2] In October 2014, Amgen’s Biologics License Application for blinatumomab was granted priority review designation by the FDA, thus establishing a deadline of May 19, 2015 for completion of the FDA review process.[3]

Structure and mechanism of action[edit]

Blinatumomab linking a T cell to a malignant B cell.

Blinatumomab enables a patient's T cells to recognize malignant B cells. A molecule of blinatumomab combines two binding sites: a CD3 site for T cells and a CD19 site for the target B cells. CD3 is part of the T cell receptor. The drug works by linking these two cell types and activating the T cell to exert cytotoxic activity on the target cell.[4] CD3 and CD19 are expressed in both pediatric and adult patients, making blinatumomab a potential therapeutic option for both pediatric and adult populations.[5]

Therapeutic use[edit]

Clinical trials[edit]

In a phase 1 clinical study with blinatumomab, patients with non-Hodgkin's lymphoma showed tumor regression, and in some cases complete remission.[6] There are ongoing phase 1 and phase 2 clinical trials of blinatumomab in patients with acute lymphoblastic leukemia (ALL).[7] One phase II trial for ALL reported good results in 2010 and another is starting.[8]

Adverse effects[edit]

Common side effects observed in Phase 2 trials are listed below; they were temporary and typically occurred during the first treatment cycle:[5]

  • Flu-like symptoms (i.e. fever, headache, and fatigue)
  • Tremor
  • Weight increase
  • Hypokalemia
  • Decrease of blood immunoglobulin

CNS effects were also observed during clinical trials and were treated via a lower dose of blinatumomab, administration of dexamethasone, or treatment discontinuation. Because the side effects were reversible, early monitoring for the CNS symptoms listed below is important:[5]

  • Seizure
  • Encephalopathy
  • Tremor
  • Apraxia
  • Speech disorders
  • Disorientation

Less common side effects include cytokine release syndrome and immunogenicity.[5]

References[edit]

External links[edit]